We have examined thymic influence on the MHC-specificity expressed by functionally and phenotypically distinct T cell subsets. Studies on thymocytes from genetically defective scid mice have suggested that TcR(gamma-delta) cells may play a critical role in promoting the entry of thymocytes into the CD4/CD8 differentiation pathway. Studies on CD4-CD8- thymocytes that express TCRalpha-beta have revealed that they are most likely an end stage cell type, rather than a precursor phenotype. In other studies, we have found that tolerance to self antigens can be induced in the thymus by either clonal deletion or clonal inactivation.